The cyclin-like protein SPY1 overrides reprogramming induced senescence through EZH2 mediated H3K27me3

被引:3
作者
Lubanska, Dorota [1 ]
Qemo, Ingrid [1 ]
Byrne, Megan [1 ]
Matthews, Kaitlyn N. [1 ]
Fifield, Bre-Anne [1 ]
Brown, Jillian [1 ]
da Silva, Elizabeth Fidalgo [1 ]
Porter, Lisa A. [1 ]
机构
[1] Univ Windsor, Dept Biomed Sci, Windsor, ON, Canada
基金
加拿大健康研究院;
关键词
cell cycle genes; cellular reprogramming; cellular senescence; histone H3 methyltransferase; induced pluripotent stem cells; PLURIPOTENT STEM-CELLS; DEVELOPMENTAL REGULATORS; HUMAN FIBROBLASTS; MOUSE; PHOSPHORYLATION; GENERATION; EXPRESSION; POLYCOMB; PATHWAY; CDK2;
D O I
10.1002/stem.3453
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Fully differentiated cells can be reprogrammed through ectopic expression of key transcription factors to create induced pluripotent stem cells. These cells share many characteristics of normal embryonic stem cells and have great promise in disease modeling and regenerative medicine. The process of remodeling has its limitations, including a very low efficiency due to the upregulation of many antiproliferative genes, including cyclin dependent kinase inhibitors CDKN1A and CDKN2A, which serve to protect the cell by inducing apoptotic and senescent programs. Our data reveals a unique cell cycle mechanism enabling mouse fibroblasts to repress cyclin dependent kinase inhibitors through the activation of the epigenetic regulator EZH2 by a cyclin-like protein SPY1. This data reveals that the SPY1 protein is required for reprogramming to a pluripotent state and is capable of increasing reprogramming efficiency.
引用
收藏
页码:1688 / 1700
页数:13
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